Wound mapping system

ABSTRACT

A tissue mapping system comprising a two dimensional array of test electrodes  10  for application to the surface of tissue under investigation and circuit means  50 - 66  for measuring an electrical characteristic of the tissue underlying each test electrode. In one embodiment the electrical characteristics is the impedance of the tissue underlying each test electrode.

This invention relates to a system and method for mapping tissue,especially but not limited to the mapping of a skin wound.

Wound measurement appears to be the only method clinicians have indetermining the state of a wound or to assess the effectiveness of agiven treatment or dressing, indeed it has been reported that inclinical trials, wound area is the most commonly reported property ofwounds¹. Although current methods are numerous, almost all are simpleand most are subjective, bringing their accuracy into question.

The most frequently used techniques are two-dimensional and includelinear measurements, wound tracing, planimetry, andstereophotogrammetry.

Linear measurements are perhaps the most simple and involve length andwidth measurements, taken at the longest length of the wound and thewidest width, measured perpendicular to the length axis² using a woundgauge or ruler. While clearly quick and inexpensive this method is verysubjective and will therefore result in a certain degree of inaccuracy.

A second linear measurement often used in the assessment of wounds isthat of area. Several manufacturers to the health care industry haveproduced a gauge with concentric circles which can be used to estimatewound area. However, as very few wounds will be perfectly circular thismethod will introduce a large amount of error into the result. Even incases where symmetry is evident, subjective identification of the woundboundary can cause inaccuracies in this method.

Planimetry, wound tracing or the acetate method is the technique whichemploys the use of metric graph paper with a 4 cm grid size where thecomplete squares within the traced wound area are counted and the resultindicated in square centimetres².

A further 2-dimensional technique used to determine wound parameters isthat of stereophotogrammetry, a more complex and expensive methodinvolving the use of a video camera attached to a computer withappropriate software. The wound is captured on video after a targetplate has been placed on the plane of the affected area. The targetplate allows correct orientation and distortion correction in order toobtain a true image of the wound before it is downloaded to thecomputer. The wound area can then be traced from the displayed image andthe software calculates the wound length, width and area². The improvedaccuracy of this method and the ability to record results in a databasemakes it more advantageous than previous techniques but its expense is alimitation.

While a study by Kantor¹ suggests that these methods are adequate indetermining wound parameters, the need to remove dressings and bandagesin order to obtain the measurements remains a crucial shortfall. Whilethere is an obvious necessity to renew and replace dressings from ahealth point of view, the frequency of replacement can have an effect onthe state of the wound. Continual agitation of the wound area does notencourage healing and removal of adhesive dressings can serve to disruptthe formation of new tissue. Therefore it would be desirable to developa method of wound measurement which did not require the removal ofdressings to calculate the chosen parameters.

An accurate, atraumatic mapping technique would have the very attractiveadvantage of enabling scientific assessment of the efficacy of varioustreatments claimed to promote/enhance wound healing and the unequivocalidentification of those most effective.

The skin has several functions including temperature regulation,immunity and protection and when the integrity of the skin is comprisedby trauma it is said to be wounded.

Wounds vary in severity and this is gauged mainly by the depth orpenetration of the injury and the skin layers involved. Minor abrasionswhere the portion of skin lost does not extend beyond the epidermis intothe dermis is defined as an epidermal wound, while deep wounds areinjuries where substantial tissue loss is evident into the lower dermallayers.

The skin's ability to replace itself goes some way to explaining thedefinition of wound healing. The CREST guidelines on ‘Principles ofCaring for Patients with Wounds’, published in 1998 defines healing inthe pathological context, as ‘ . . . the body's replacement of destroyedtissue by living tissue³. The onset of an injury triggers a series ofcellular and biochemical events from the biological and immunologicalsystems whereby an organised pathway of processes results in a healedwound.

The healing process can be divided into 4 sequential but not distinctphases, haemostasis, inflammation, proliferation and maturation.Haemostasis is the process of stopping bleeding⁴ which is a commonoccurrence in deep tissue trauma; following injury a discharge of bloodor fluid from a vessel in the surrounding tissue (extravasation)initiates blood clotting and platelet activation. It is this plateletactivation which triggers haemostasis, vasoconstriction and new tissueformation to aid in wound repair. The vasoconstriction is a result ofthe release of a series of chemical mediators such as histamine,serotonin and adenosine triphosphate (ATP). Their role is to attract thecirculating leucocytes (colourless blood component which protectsagainst micro organisms) to the site of impact⁴. The onset ofvasoconstriction also coincides with the start of the second orinflammatory phase.

The increased volume of ‘local’ blood allows plasma to leak to thesurrounding tissue thus swelling them, hence inflammation. Neutrophilsand monocytes arrive at the wound dormant and on activation theneutrophils set about removing any offensive bacteria while themonocytes become macrophages producing growth factors to accelerate thehealing process. Macrophages themselves also phagocytose pathogenicorganisms and clear tissue debris. The last stage of this phase sees thereleased growth factors stimulating endothelium to oversee the growth ofnewly formed blood vessels.

The third stage, the proliferation phase is the growth and reproductionof tissue, namely connective or granulation tissue whose formation isdependent on the newly formed blood vessels. The blood vessels provide asuitable environment for tissue regeneration by providing nutrients andoxygen for the cells. Firstly fibroblasts create a network of collagenfibres in the wound bed and produce a sticky substance, proteoglycanwhich fills the tissue bed binding the fibres together to form a stableframework. Epithelialisation and contraction are the final processes inthis stage whereby the wound regenerates epithelium from the outer edgesof the wound towards the centre. The cells migrate across the surface tothey meet and at the same time the wound is contracted bymyofibroblasts.

The fourth and final phase of the healing process is the maturationphase which can be several weeks from the time of injury and involvesthe remodelling of the collagen fibres laid down in the proliferationphase⁴. This collagen is soft and gelatinous and is replaced in thisstage by more orderly and stronger collagen. The final act in thehealing process is the removal of fibroblasts from the wound site andthe restructuring of blood vessels away from the area which results inthe shrinking and paling of the scar tissue⁴.

The skin is made up of 3 main layers:—the subcutaneous layer, thedermis, and the epidermis (the strongest layer)⁵.

The epidermis, the outermost layer, is in direct contact with theenvironment and therefore provides a protection barrier to outsidematerials (products, water, etc.) as well as filtering sunlight. Unlikeany other organ of the body, the epidermis is self-renewing and hencereplaces itself continually⁶.

The epidermis can be sub-divided into several further layers with thestratum corneum forming the outermost layer. Cells in the underlyingbasal layer are constantly multiplying and undergo changes as they pushup towards the skin's surface. As these cells become flattened,compacted and dehydrated, they lose their nuclei and develop a hardeningprotein, eventually forming the stratum corneum. The dead cells on thesurface are continuously being shed, replaced by the cells migratingfrom the underlying layers⁷.

The stratum corneum consists of several layers of dead cells and variesin thickness depending on location on the body, the thickest layersbeing on the palms of the hand and the bottom of the feet. The stratumcorneum becomes thicker with age and exposure to the elements making itmore susceptible to wrinkles and creases⁵.

The relatively non-conductive stratum corneum sandwiched between aconductive electrode interface and the conductive hydrated underlyingtissue acts as a dielectric between two plates as in a capacitor.Therefore the stratum corneum's electrical properties is oftenrepresented by a simple capacitor, C_(P) ⁸.

Some ions do however traverse the stratum corneum barrier and this isrepresented, along with the capacitance, by a large parallel resistance,R_(P).

The tissues underlying the skin are conductive and can be represented bya resistance, R_(T), in series with the above parallel combinations. Theequivalent circuit model is shown in FIG. 1. This equivalent circuitmodel comprising simple resistances and a capacitance is obviously asimplification of the skin's complex electrical properties.

At very high frequencies, the impedance of the capacitance tends to zeroand the overall impedance approaches that of R_(T). At low frequency theimpedance of the capacitance tends to infinity and current thereforeflows through the series combination of R_(T) and R_(P) and the overallimpedance is generally therefore much larger than the high frequencycase.

Theoretically the impedance locus of the ‘classical’ model (equivalentcircuit incorporating a resistance and capacitance in parallel) shouldconsist of a semi-circular arc whose centre is located exactly on thereal axis, as shown on FIG. 2.

However, FIG. 3 shows the typical form of a measured impedance locusplot of the electrode-skin interface, demonstrating that the simplemodel described above is not adequate to fully characterise theelectrical properties of the skin.

R_(inf) and R_(o), the intercepts with the real axis at high and lowfrequencies respectively, are the high and low frequency limitresistances. The depression of the centre of the arc below the axis, isexpressed in terms of the angle φ. ω_(o) (=2πf_(o)) is the angularvelocity of the ‘peak’ of the arc. This is the point with the largestvalue of reactance, X_(S) ⁶.

Impedance loci such as the one above have been found to be well modelledby the formula derived by Cole in 1940¹⁰ (equation1). [Othermathematical models are possible].Z=R _(∞)+(R ₀ −R _(∞))/[1+jω/ω ₀)^(α)]  (1)

The expression is used to describe the complex impedance of certainbiological tissues. α is dimensionless and has a value 0<α≦1 and isrelated to φ such that φ=απ/2. When α=1, the impedance locus is asemi-circular arc whose centre lies on the real axis with a frequencyintercept angle φ of 90°. When α<1, as is normally the case, the locustakes the form of a ‘depressed’ semi-circular arc whose centre liesbelow the real axis and the frequency intercept angle φ is less than90°.

The complex impedance described by the Cole equation (1) corresponds toseveral equivalent circuits. FIG. 4 shows one such circuit.

Z_(cpa) is an empirical, constant phase angle impedance which shunts theresistance R_(p) where:Z _(cpa) =K(jω)^(−α)  (2)K is a measure of the magnitude of Z_(CPA) (i.e. K=|Z_(CPA)|_(ω=1)) andhas units of Ωs^(−α). These circuit elements can be expressed in termsof the Cole parameters R_(∞), R₀, ω₀ and α, as follows:R _(p)=(R ₀ −R _(∞))  (3)K=(R ₀ −R _(∞))/T ₀ ^(α) =Rp/T ^(α).  (4)R _(T) =R _(∞)  (5)

It can be readily appreciated that when the stratum corneum at a givenskin site is punctured, abraded or absent (as a consequence of trauma ordisease, for example) the measured low-frequency impedance at the sitewill be dramatically reduced due the absence of the large stratumcorneum impedance (represented in the simplest case (FIG. 1) by theparallel combination of the skin's capacitance and resistance, C_(P) andR_(P)). Only the small resistance, R_(T), of the underlying tissue willremain.

Mapping, for example, the low-frequency impedance of skin sites in andaround a wound site will evidence clearly the major differences betweenhealthy skin (high impedance) and the wound (low impedance).

It is therefore an object of the invention to provide an improved systemand method of mapping tissue, in particular but not exclusively skinwounds.

Accordingly, the present invention provides a tissue mapping systemcomprising a set of test electrodes for application to the surface oftissue under investigation and circuit means for measuring an electricalcharacteristic of the tissue underlying each test electrode.

Preferably the system further includes means for displaying saidmeasured characteristics and/or derivative(s) thereof in human-readableform.

Preferably, too, the electrical characteristic is the impedance of thetissue underlying each test electrode.

The invention further provides a method of mapping tissue comprisingapplying a set of test electrodes to the surface of tissue underinvestigation and measuring an electrical characteristic of the tissueunderlying each test electrode.

The invention further provides a wound dressing incorporating a set oftest electrodes for application to the surface of wound tissue andcircuit means for measuring an electrical characteristic of the tissueunderlying each test electrode.

An embodiment of the invention involves the use of a ‘smart’ wounddressing which can be used to monitor the skin's electrical impedanceand thus to assess the size, shape, depth and composition of the wound,all without the need of removing the dressing. The principle of thisembodiment is illustrated diagrammatically in FIG. 5, where theelectrode connecting leads are omitted for clarity.

If an array of test electrodes 10, incorporated in a wound dressing 12,is located over a wound site 14 in intact skin 16, the individualimpedances of the tissue underlying each test electrode 10 can be usedto create a two-dimensional map of the wound. If a sufficient number ofsmall area electrodes are used, the shape and size of the wound can beascertained from the measured impedance values. Over time, changes inthe wound shape and size can be followed using this technique.

It is possible to model the electrical properties of tissues withequivalent electrical circuits. With the correct choice of mathematicalor equivalent circuit model, it is possible to relate the model elementsto the underlying physical processes and thus study the healingprocesses and meaningfully assess the efficacy of a range of therapies.

The use of a multi-electrode array enables the monitoring of differentsites without the need to move a single electrode from one measurementsite to the next.

Hydrogel is presently used as a wound dressing as it protects the woundbed from foreign contaminants, and hydrates and enhances the environmentessential to thorough wound healing. Hydrogels can also be used in theconstruction of bio-impedance monitoring electrodes and, along with theuse of screen printing or similar technologies, lend themselves to thefabrication of accurate, flexible, low-profile electrode arrays. Thetest electrodes can therefore be incorporated into a hydrogel-basedwound dressing and used to monitor the wound and the effect of therapywithout the need to remove the dressing. A significant improvement oncurrent techniques is that this system does not interfere with the woundbed. As the preferred embodiment is designed to be used as part of, orto constitute, the wound dressing, it allows new tissue formed as partof the healing process, to remain undisturbed while the wound is beingassessed. In addition to calculating the wound area, this device is alsoeffectively assisting wound healing.

Most of the prior art discussed above produce wound parameters likelength and width and at best volume values, but none, with the exceptionof the stereophotogrammetry, produce a map or picture of the wound. Evenusing stereophotogrammetry the wound parameters must be calculated fromthe picture after the wound photograph has been ‘traced’ around usingthe computer. This method can be inaccurate due to the difficultiesassociated with capturing a real size image of the wound to download.

In one embodiment, the invention maps the wound direct from the site andproduces an image, complete with calculations of area, tissue type etc.,on a computer screen with little involvement from the clinicianrequired, therefore reducing subjectivity and error.

As a wound heals, particularly a full thickness wound, it passes throughseveral phases or stages where new tissue and eventually skin will form.Therefore another indication of wound healing is the tissue type presentin the wound bed. It is possible to model the electrical properties oftissues with mathematical and/or equivalent electrical circuits. Withthe correct choice of mathematical or equivalent circuit model, it ispossible to relate the model elements to the underlying physicalprocesses and thus study the healing processes and meaningfully assessthe efficacy of a range of therapies.

The invention therefore allows a clinician to characterise tissue andhence evaluates the tissue type present under the individual electrodesincorporated in the dressing. This information can then be used toestablish the state of the wound.

Due to the severity of some full thickness wounds, many sores will notheal without some form of intervention. Several treatment techniques areemployed the use of drugs, wound dressings and the application ofelectrical signals. Any affect that these techniques have on woundhealing can ideally be assessed using electrical impedance spectroscopy(EIS). The application of electrical fields (DC, pulsed, etc.) has beenreported to promote wound healing^(11,12,13). Unfortunately, due to thedifficulties in assessing wound healing, it has not been possible toestablish clearly the best ‘electrical therapy’. This shortcoming can beaddressed with the use of the impedance array as the test electrodes canbe used to apply the desired ‘electrotherapeutic’ signals and toevaluate their effects, all without removing the dressing. The testelectrodes can also be used for iontophoretic drug delivery andassessment of resultant therapeutic effect or tissue trauma.

An embodiment of the invention will now be described, by way of example,with reference to the accompanying drawings, in which:

FIGS. 1 to 4 (previously described) are diagrams illustrating theelectrical properties of the human skin;

FIG. 5 (previously described) is a schematic diagram illustrating thegeneral principles of an embodiment of the invention;

FIG. 6 is a schematic circuit diagram illustrating theimpedance-measuring principle used in the present embodiment;

FIG. 7 is a plan view of a 5×5 rectangular array of test electrodes usedin an embodiment of the invention;

FIG. 8 is a cross-section through the array of test electrodes taken onthe line X-X of FIG. 7, the array being incorporated in a wounddressing;

FIG. 9 is a block diagram of a wound mapping system using the array ofFIG. 7; and

FIG. 10 illustrate alternative forms of test electrode arrays.

Referring first to FIGS. 7 and 8, a rectangular 5×5 array of testelectrodes 10 is screen printed onto a thin flexible insulatingsubstrate 18, each test electrode 10 having a respective lead 20 alsoscreen printed on the substrate. Screen printing enables the accuratepatterning and positioning of the electrodes and their associated leads.The leads 20 are preferably formed using a conductive material such as aserigraphic silver-loaded ink (e.g. PF-410 silver conductive ink fromNorcote, England) and the test electrodes 10 are preferably formed usinga serigraphic silver/silver chloride-loaded ink to ensure goodelectrical performance at the electrode-gel interface (e.g. Part No.5874 from Dupont, Bristol, England). Other materials may be used if theelectrodes are also to be used apply iontophoretic or other therapeuticelectrical signals as will be described. All twenty-five test electrodeleads 20 are brought together at a projecting connector edge 26 of thesubstrate 18.

A number of reference electrodes 22 are also screen printed on thesubstrate 18. In the present case six substantially parallel strip-likereference electrodes 22 are provided, four of which extend each betweena respective pair of adjacent columns of five test electrodes 10 and twomore of which are applied on the outsides of the test electrode array.The six reference electrodes 22 are connected together in common by across lead 24, and a single further lead 28 connects all the referenceelectrodes 22 to the connector edge 26.

An insulating layer 30 (FIG. 8) is deposited on each lead 20, 24 and 28to avoid electrical shorting (e.g. dielectric ink SD2460 Flex Komp A & Bfrom Norcote, England). However, several millimetres of each lead 20, 28is exposed at the connector edge 26 for connection to drive circuitry(FIG. 9). The substrate 18 may be CT4 heat stabilised polyestersubstrate from Autotype, Wantage, England. The substrate 18 isincorprated in a wound dressing 12.

The substrate 18 can be one continuous sheet or be perforated or cutinto ‘finger-like’ peninsulas to enhance flexibility and enable moistureto escape where necessary. A backing of suitable material (e.g. 1.6 mmadhesive foam, 8104/800C from Medifix, Luton, England) can be used, ifnecessary, to hold the ‘finger-like’ peninsulas together and easeapplication.

A hydrogel layer 32 is used as an electrode gel as hydrogels are welltolerated by the skin and are currently used in wound dressings (e.g. SW200 or SW 206 hydrogels from First Water, Ramsbury, England). A singlesheet of hydrogel 32 can be used to cover all the test and referenceelectrodes 10, 22 and their leads, as shown in FIG. 8, or individualhydrogel ‘pads’ can be placed over each test and reference electrode. Inthe case of a single hydrogel sheet, the electrodes and their respectiveoverlying regions of gel can effectively be electrically separated fromone other by rendering intervening sections of the hydrogel relativelynon-conductive. This can be achieved during the manufacture of thehydrogel or by treating the hydrogel sheet with, for example, heatedblades which selectively dry portions of the hydrogel sheet. In anyevent, whatever technique is used, the electrical resistance betweenadjacent electrodes should be high relative to the resistance via thegel between each electrode and the underlying tissue.

Generally, the more test electrodes in the array the better theresolution. The optimum number will depend on the given application, thesize of the wound under study and the mapping accuracy required. Atypical range is a rectangular array of from 5×5 to 100×100 electrodesdepending on application and wound size. For certain routine clinicalmonitoring applications as few as two test electrodes may be sufficient.Typical test electrode sizes range from 1 mm×1 mm to 1 cm×1 cm. A rangeof electrode arrangements are possible for Impedance measurement. Thebest will depend on the given application.

Before describing the drive circuitry for the electrode array of FIGS. 7and 8, several techniques for measuring the electrical characteristicsof tissue will first be described.

If the same two electrodes are used to inject current and to measure theresultant voltage (or vice versa), this is termed the 2-electrodetechnique. In this case, the impedances of the two electrode-skininterfaces are measured in series with that of the underlying tissuebetween them.

A 4-electrode technique involves injecting current via a different pairof electrodes to those used to detect the voltage. In theory this avoidscontributions from the four electrode-skin interfaces and one shouldtherefore optimally observe the properties of the tissue between thevoltage detecting electrodes.

A 3-electrode technique exists which enables one to study the propertiesof an individual interface without contributions from the otherelectrodes or the bulk of the sample. This technique is ideally suitedto study the impedance of one single electrode-skin site.

Based on the above, the electrode technique preferred for use in woundmapping in the present embodiment is the three electrode technique (FIG.6). This involves the use of a test electrode 10 through which analternating current is passed and a ‘back’ electrode 34, usuallypositioned on the opposite side of the body segment under investigation,to complete the current loop. A reference electrode 22 positioneddirectly beside the test electrode 10 effectively senses only thepotential V₁ dropped across the electrode-skin impedance under test, Z₁.

The potential ΔV detected by the high input impedance voltmeter measuresthe following:ΔV=V ₁ +V ₁₋₂ +V ₂ =I ₁ Z ₁ +I ₂ Z _(dermis) +I ₂ Z ₂  (6)

As the voltmeter used contains an instrumentation amplifier with anextremely high input impedance, the current I₂ flowing through it (andthe impedances Z_(dermis)+Z₂) will be negligibly small. The voltagesV₁₋₂ and V₂ measured across the tissue impedance and the site below thereference electrode, respectively, will therefore also be negligible. Asa result, the measured voltage difference ΔV is solely equal to thevoltage drop V, across the test electrode-skin impedance underinvestigation. The electrode-skin interface impedance Z₁ under study issimply obtained by dividing the measured voltage drop ΔV by the appliedcurrent I.

In the present embodiment, as shown in FIG. 7, a single referenceelectrode 22 is common to a plurality of test electrodes 10. Thisarrangement has the advantage of not requiring changes in connection tothe reference electrodes while impedance measurements are carried outfrom one test electrode in the array to another. A further advantage isthat the long fine amalgamation of the reference electrodes takes upless space on the electrode array, thus maximising the surface coveredby test electrodes in the array. Although the back electrode 34 isgenerally best positioned on the opposite side of the body site underinvestigation, it can be incorporated into the array for ease of use. Inthis case it can be, for example, a long electrode screen printed on thesubstrate 18 around the peripheral edge of the array (not shown).

The test electrodes 10 forming the arrays may be rectangular, as in FIG.7, circular or any other form which is best suited for a givenapplication and which lends itself best to the fabrication technique.The distribution of the test electrodes in the arrays may be regular orirregular, as required by the given application and algorithms used. Forexample, the test and reference electrodes may be a series of concentriccircles, FIG. 10 a, or the test electrodes may be disposed between the“spokes” of a wheel-like reference electrode, FIG. 10(b). Alternativelythe test electrodes may be disposed between concentric referenceelectrodes, FIG. 10(c). Obviously many permutations are possible. InFIG. 10 the leads to the test and reference electrodes are not shown forclarity. Connecting leads can be either be (i) interlaced around otherelectrodes, (ii) deposited in layers interspaced with dielectricinsulating layers to enable the crossing over of the leads withoutelectrical shorting or (iii) ‘through-hole-plated’ to the reverse sideof the substrate so that the leads avoid the side with the depositedelectrodes.

Referring now to FIG. 9, in use the 5×5 array of electrodes 10 isconnected to a rotary switch 50 by a ribbon connector 52. The ribbonconnector 52 has twenty-six conductors, one each connected individuallyto each of the twenty-five test electrodes 10 and one connected incommon to all six reference electrodes 22. At the electrode array endthe connection is made by a crimp connector 54 to the exposed ends ofthe leads 20, 28 at the substrate connector edge 26, while at the rotaryswitch the connection is made by a 26-way DIN connector 56. The rotaryswitch has two output lines 58 and 60. The former is permanentlyconnected to the reference electrode lead 28. The latter is selectivelyconnectable individually to any one of the test electrodes 10, accordingto the rotary position of the switch 50.

The lines 58, 60 are connected to respective inputs of an interfacecircuit 62, which also has an input from the back electrode 34. AnImpedance analyser 64 is connected to the electrode array via theinterface circuit 62 and the rotary switch 50. For each position of theswitch 50 the impedance analyser 64 is actuated to generate analternating test current and measure the resulting impedance of thetissue under the currently selected test electrode 10 according to theprinciples described with reference to FIG. 6. The impedance analyser 64may comprise a Solartron 1260 Impedance/Gain Phase Analyser marketed bySolartron Analytical, Famborough, Hampshire, England. The interfacecircuit 62 limits the test electrode current to acceptable levels incase of malfunction or inappropriate setting of the analyser 64.

The results of the analysis can be displayed directly as a wound mapimage on a video display device 66. In other words, the impedance valuesderived from the rectangular 5×5 (or other size) matrix of testelectrodes 10 are displayed as corresponding colours, shades ornumerical values on the device 66 in a similar matrix whose individuallocations correspond to those of the electrode array. The results canalternatively or additionally be output on other forms of human-readabledisplay devices, such as printers or plotters.

For each test electrode the measurement may be made at one AC frequencyor measurements can be made at each of a plurality of frequencies,depending upon the application and output requirement. In general asuitable range of frequencies is from 1 milliHz to 100 kHz, preferablyfrom 1 Hz to 50 kHz, although where a measurement is made at only asingle frequency a value towards the lower end of the latter range ispreferred.

As discussed, the test electrodes 10 may be used to apply iontophoreticor other therapeutic electrical signals to the wound. In that case asuitable therapeutic signal generator 68 is connected to the interfacecircuitry 62, and the latter contains switching circuits which switchover from the impedance analyser 64 to the signal generator 68 when itis desired to apply such therapy.

In a modification of the above embodiment, separate reference electrodes22 are not used. Instead, during measurement on any selected testelectrode 10 an adjacent test electrode acts temporarily as itsreference electrode. Thus the particular test electrode actingtemporarily as the reference electrode for any given test electrodeundergoing measurement would be connected by the rotary switch 50 to theline 58 in FIG. 9.

An advantageous feature of the embodiment is the possible use of the4-electrode technique by appropriate connection to sets of any fourelectrodes in the array. The 4-electrode technique enables the study ofthe underlying tissue Impedance and can be used to assess the tissuewithin the wound. Inter-electrode distances influence the depth theelectric field penetrates into the tissue and hence these can be chosento study differing depths of the wound. In electrode arraysincorporating many small area electrodes, combinations can be chosen tostudy and map the wound site for a range of penetration depths.

Obviously a suitably wide frequency range (typically from Megahertz toMillihertz) should be used and a sufficiently large number of datapoints obtained if a complete characterisation is required for researchpurposes. For routine clinical use of the invention, one or severalstrategically chosen frequency measurements may be all that is requiredfor a given application. The applied signal amplitude for impedancemeasurement should be such as to ensure that the resultant currentdensity is low, ensuring electrical safety and skin impedance linearity.

For research purposes, for example, to study the effects ofelectromagnetic fields on wound healing, one may be interested inmeasuring the skin or tissue impedances over a wide frequency rangeusing numerous frequencies. Maps of the calculated parameters ofmathematical models (e.g. Cole equation (equation 1)) or equivalentcircuit models (e.g. FIG. 4) may then be presented on a monitor screenor printed for records. Alternatively, for example, the areas ofspecific regions as revealed by impedance parameters, ratios ofparameters or other calculations involving such parameters may becalculated and presented, dispensing with the need to present, inspectand interpret maps.

Maps of calculations based on the following can be used to highlightdifference regions in the wound site and differences in the tissuesinvolved:

-   (i) Magnitude of the impedance (or admittance or similar electrical    property) (modulus, real and imaginary components) and phase angle    measured at a given frequency.-   (ii) Ratios of the above where two or more such measurements are    carried out at different frequencies. Other mathematical    calculations are also possible.-   (iii) Mathematical model parameters (e.g. Cole model) and ratios or    other mathematical calculations involving such parameters.-   (iv) Equivalent circuit parameters and ratios or other mathematical    calculations involving such parameters.

For Intact skin, the impedance measured at a low frequency is dominatedby the skin impedance rather than that of the underlying tissue. Maps ofa wound site can therefore be simply obtained by mapping the siteimpedances measured at one single frequency, thus greatly simplifyingthe procedure.

If, based on research, only one model parameter is of interest for agiven application, only two or three measurement frequency points willbe required. For example, the calculation of K, a and Rp in theequivalent circuit model shown in FIG. 4 will require the use of atleast two frequencies, more if high accuracy is required.

A suitably designed impedance array according to the precedingprinciples can be used to study the electrical properties of otherorgans/structures such as the heart or brain. Arrays of very smallelectrodes (e.g. in the micrometer range) can be fabricated using thinfilm techniques unto flexible substrates. In the case of the heart,areas of ischaemia may be detected, characterised and mapped using thisinvention.

The invention is not limited to the embodiments described herein and maybe modified or varied without departing from the scope of the invention.

REFERENCES

-   1. Kantor, J., Margolis, D. J., ‘Efficacy and Prognostic Value of    Simple Wound Measurements’, Arch. Dermatol. 1998; 134:1571-1574.-   2. Langemo, D. K., Melland, H:, Hanson, D., Olson, B., Hunter, S.,    Henly, S. J.; ‘Two-Dimensional Wound Measurement: Comparison of 4    Techniques’, Advances in Wound Care 1998; 11:337-343.-   3. CREST, Guidelines on the General Principles of Caring for    Patients with Wounds, 1998.-   4. S. Bale and V. Jones, Wound Care Nursing—A patient-centred    approach: Bailliere Tindall, 1997.-   5. www.naturesrain.com/theskin.htm, 1997.-   6. Lackermeier, A. H., McAdams, E. T., Moss, G. P., Woolfson, A. D.;    ‘In vivo A. C. Impedance Spectroscopy of Human Skin: Theory and    Problems in Monitoring of Passive Percutaneous Drug Delivery’,    Annals of the New York Academy of Sciences 1999; 873:197-213.-   7. J. Jossinet and E. T. McAdams, “The Skin/Electrode Interface    Impedance,” Innovation and Technology in Biology and Medicine, vol.    12, pp. 22-31, 1991.-   8. Lackermeier, A. H.; ‘A novel multi-channel Impedance analyser for    the in vivo investigation of the electrical properties of human skin    during transdermal drug delivery’, Ph.D. Thesis 2000.-   9. McAdams, E. T., Jossinet, J.; ‘The importance of electrode-skin    impedance in high resolution electrocardiography’, Automedica 1991;    13:187-208.-   10. Cole, K. S.; ‘Permeability and impermeability of cell membranes    for ions’, Cold Spring Harbor Symp. Quant. Biol. 1940; 8:110-112.-   11. K. M. Bogie, S. I. Reger, S. P. Levine, and V. Sahgal,    “Electrical stimulation for pressure sore prevention and wound    healing,” Assistive Technology, vol. 12, pp. 50-66, 2000.-   12. G. D. Mulder, “Treatment of Open-Skin Wounds with    Electric-Stimulation,” Archives of Physical Medicine and    Rehabilitation, vol. 72, pp. 375-377, 1991.-   13. S. I. Reger, A. Hyodo, S. Negami, H. E. Kambic, and V. Sahgal,    “Experimental wound healing with electrical stimulation,” Artificial    Organs, vol. 23, pp. 460-462, 1999.

1-30. (canceled)
 31. A tissue measurement system comprising atwo-dimensional array of test electrodes for application to the surfaceof tissue under investigation, circuit means for measuring an electricalcharacteristic of the tissue underlying each test electrode, and meansfor presenting at least one value representing a physical characteristicof at least one region of tissue based upon the measured electricalcharacteristics.
 32. A system as claimed in claim 31, wherein thephysical characteristic is area.
 33. A system as claimed in claim 32,wherein the presenting means presents a plurality of values on a displaydevice to provide a visual map representing the physical extent of theregion of tissue.
 34. A system as claimed in claim 31, wherein the arrayof test electrodes is arranged on a flexible backing of insulatingmaterial.
 35. A system as claimed in claim 34, wherein the array ofelectrodes is a rectangular array.
 36. A system as claimed in claim 34,wherein each test electrode is covered with a conductive gel, theresistance between adjacent test electrodes being high relative to theresistance via the gel between each test electrode and the underlyingtissue.
 37. A system as claimed in claim 36, wherein the gel ishydrogel.
 38. A system as claimed in claim 34, wherein leads for thetest electrodes are also disposed on the flexible backing of insulatingmaterial and covered with an insulating material.
 39. A system asclaimed in claim 31, wherein the two-dimensional array comprises atleast 25 test electrodes.
 40. A system as claimed in claim 31, whereinthe electrical characteristic is the impedance of the tissue underlyingeach test electrode.
 41. A system as claimed in claim 31, wherein thecircuit means measures the electrical characteristic by applying analternating electrical signal between the test electrode and at leastone other electrode applied to the organic body of which the tissueforms a part.
 42. A system as claimed in claim 41, wherein the circuitmeans measures the electrical characteristic by measuring the voltagebetween each test electrode and an adjacent reference electrode alsoapplied to the tissue.
 43. A system as claimed in claim 42, wherein thereference electrode is also disposed on the flexible backing ofinsulating material.
 44. A system as claimed in claim 43, wherein asingle reference electrode is common to a plurality of test electrodes.45. A system as claimed in claim 43, wherein during measurement on agiven test electrode an adjacent test electrode acts temporarily as itsreference electrode.
 46. A system as claimed in claim 41, wherein thesaid at least one other electrode is also disposed on the flexiblebacking of insulating material.
 47. A system as claimed in claim 41,wherein for each test electrode a measurement is made at a plurality ofdifferent frequencies.
 48. A system as claimed in claim 41, wherein theor each measurement is made at a frequency of from 1 milliHz to 100 kHz.49. A system as claimed in claim 31, wherein the array of testelectrodes is incorporated into a wound dressing.
 50. A method ofmeasuring tissue comprising applying a two-dimensional array of testelectrodes to the surface of tissue under investigation, measuring anelectrical characteristic of the tissue underlying each test electrode,and presenting at least one value representing a physical characteristicof at least one region of tissue based upon the measured electricalcharacteristics.
 51. A method as claimed in claim 50, wherein thephysical characteristic is area.
 52. A method as claimed in claim 51,wherein a plurality of values are presented on a display device toprovide a visual map representing the physical extent of the region oftissue.
 53. A method as claimed in claim 50, wherein the array of testelectrodes is arranged on a flexible backing of insulating material. 54.A method as claimed in claim 53, wherein each test electrode is coveredwith a conductive gel, the resistance between adjacent test electrodesbeing high relative to the resistance via the gel between each testelectrode and the underlying tissue.
 55. A method as claimed in claim50, wherein the two-dimensional array comprises at least 25 testelectrodes.
 56. A method as claimed in claim 50, wherein the electricalcharacteristic is the impedance of the tissue underlying each testelectrode.
 57. A method as claimed in claim 50, wherein the electricalcharacteristic is measured by applying an alternating electrical signalbetween the test electrode and at least one other electrode applied tothe organic body of which the tissue forms a part.
 58. A method asclaimed in claim 57, wherein the electrical characteristic is measuredby measuring the voltage between each test electrode and an adjacentreference electrode also applied to the tissue.
 59. A method as claimedin claim 57, wherein for each test electrode a measurement is made at aplurality of different frequencies.
 60. A method as claimed in claim 50,wherein the array of test electrodes is incorporated into a wounddressing and applied to a wound.